The study of the human pupil light reflex (PLR) is important as a paradigm of neural control and as a non-invasive method for detecting pathology within the reflex arc. This grant interprets the dynamics produced by the PLR from the point of view of nonlinear dynamics. A time delay is an intrinsic property of this reflex and hence the modelling is in terms of nonlinear delay-differential equations (DDEs). Physiological considerations suggest the importance of extending earlier studies (1st-order DDE with discrete delay) 1) to a 2nd-order DDE to model the elasto-mechanical properties of the iris and its musculature, and 2) to include a distributed delay or state-dependent delay. The predictions of these models, obtained from analytical and numerical studies, will be directly compared to experimental observations of the dynamics produced when the PLR is clamped, with external electronic feedback. Noise in the PLR will be measured under open-loop conditions and analyzed for evidence of a low-dimensional strange attractor (e.g. determination of dimension and Liapunov exponent). The influence of noise on the intrinsic dynamics of the PLR will be investigated through the study of the stochastic DDE versions of the above models. The above studies will be applied to an analysis of pupil dynamics observed in patients with demyelinative optic neuropathy. Measurements of the distribution of delays (demyelination) in the optic nerve may be of value as a prognostic sign for visual loss. Moreover studies of the abnormal pupil cycling seen in optic neuritis are useful as a model for examining the consequences of demyelination on the functioning of feedback mechanisms in the central nervous system. It is anticipated that the studies in this proposal will go a long way towards understanding the nature of the dynamics (i.e. deterministic, stochastic or both) that can be generated by the nervous system in health and disease.